Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002710030 | SCV003738605 | uncertain significance | Inborn genetic diseases | 2021-10-12 | criteria provided, single submitter | clinical testing | The c.5951C>T (p.T1984M) alteration is located in exon 40 (coding exon 40) of the CUBN gene. This alteration results from a C to T substitution at nucleotide position 5951, causing the threonine (T) at amino acid position 1984 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003611627 | SCV004376617 | uncertain significance | Imerslund-Grasbeck syndrome | 2023-07-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1984 of the CUBN protein (p.Thr1984Met). This variant is present in population databases (rs150924438, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 2397431). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CUBN protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV005036627 | SCV005666260 | uncertain significance | Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign | 2024-05-16 | criteria provided, single submitter | clinical testing |